A randomized, placebo-controlled trial of betamethasone for the prevention of respiratory distress syndrome at 24 to 28 weeks' gestation

Abstract

Previous randomized controlled studies of corticosteroids for the reduction of respiratory distress syndrome have failed to demonstrate benefit in very early premature gestational age groups. A randomized, double-blind, placebo-controlled clinical trial of betamethasone given to mothers with intact membranes and threatened premature delivery between 24 and 28 weeks of pregnancy was conducted. Thirty-six patients were randomized to receive betamethasone, two doses of 12 mg, 24 hours apart, and 41 received placebo. No difference was found in the overall incidence of respiratory distress syndrome between the two groups (betamethasone vs placebo 0.55 vs 0.66) or in the incidence of respiratory distress syndrome in babies delivered between 1 and 7 days after the first dose of drug (betamethasone vs placebo 0.78 vs 0.88). Nor were there any differences observed in any measure of severity of respiratory distress syndrome between the groups. The neonatal death rates were also similar (betamethasone vs placebo 0.25 vs 0.24). The only difference seen was an unexpected reduction in the betamethasone group in the incidence of grades 3 and 4 intraventricular hemorrhage (betamethasone vs placebo 1/31 vs 9/36, p = 0.01). Therefore this study was unable to demonstrate any beneficial effect of corticosteroids in reducing respiratory distress syndrome at less than 28 weeks' gestation in spite of a sample size that had an 80% likelihood of detecting a 50% reduction in the incidence of respiratory distress syndrome with p = 0.05, which is the minimum reduction seen in virtually all randomized trials in other gestational age groups.